The Food and Drug Administration (FDA) today told 20 companies to cease marketing unapproved drug products containing ergotamine tartrate. Ergotamine tartrate products are used to treat vascular headaches, including migraines. As part of the FDA's continued efforts to combat the marketing of unapproved drugs, the agency sent warning letters to eight manufacturers and 12 distributors warning them that they are subject to further enforcement action if they do not stop manufacturing and distributing these products.

The agency urges consumers who are using ergotamine products and have questions or concerns to contact their health care provider. This action does not affect FDA-approved products containing ergotamine, which will remain on the market.

"Unapproved drugs pose real risks to the American public," said Steven Galson, M.D., director of the FDA's Center for Drug Evaluation and Research (CDER). "Because they have not been subject to FDA review, the safety, effectiveness, and quality of such products are unknown. We remain dedicated to tackling this problem through education and outreach, as well as enforcement actions like these. It is central to our mission to ensure a safe and effective drug supply for the American public."

In addition to marketing these products without FDA approval, most of the companies receiving warning letters have omitted from their drugs' labeling critical warnings regarding the potential for serious, possibly fatal, interactions with certain other drugs. Based on recent scientific information, the five marketed, approved versions of ergotamine-containing products have updated their labeling to include a box warning (the strongest agency warning) against using such products when also taking potent CYP 3A4 inhibitors, including some antifungal agents, protease inhibitors, and certain antibiotics. CYP 3A4 is a metabolic enzyme that helps the body eliminate drugs or other chemicals. Serious and life-threatening ischemia (a restriction in blood supply), including death and gangrene, have resulted when such products are used together. Most unapproved versions of the drug do not carry these warnings.

"The warning letters we issued are another example of our commitment to the Unapproved Drugs Initiative. We are taking a sensible, risk-based approach to the problem, and remain dedicated to the goal of getting unapproved drugs off the market," said CDER's Director of Compliance, Deborah M. Autor. "Doctors and patients often do not realize that not all drugs that are available on the market are backed by FDA approval. We estimate that less than 2% of prescribed drugs are unapproved. This lack of approval undermines FDA's drug safety efforts. Drugs that skirt the approval process may be unsafe, may not work, and in our experience, often have inadequate labeling."

Companies have 15 days to respond to the FDA with a discontinuation plan for their products. Manufacturers have 60 days to cease manufacturing of new product, and distributors have 180 days to cease further shipment of existing products. Previously manufactured unapproved ergotamine products may still be found on pharmacy shelves for a short period of time.

FDA's actions against unapproved drugs are part of the agency's broader initiative, announced in June 2006, to ensure that consumers and the health care community are provided with established and emerging drug safety information so that they can make the best possible medical decisions about the safe and effective use of drugs.

For additional information, including copies of the Warning Letters (which identify the firms involved and the names of their products), see FDA's Unapproved Drugs Web page, located at http://www.fda.gov/cder/drug/unapproved_drugs.